{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T14:25:35Z","timestamp":1791296735923,"version":"4.1.0"},"reference-count":74,"publisher":"American Society for Microbiology","issue":"5","license":[{"start":{"date-parts":[[2015,5,1]],"date-time":"2015-05-01T00:00:00Z","timestamp":1430438400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Infect Immun"],"published-print":{"date-parts":[[2015,5]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p><jats:named-content content-type=\"genus-species\">Leishmania donovani<\/jats:named-content>, a protozoan parasite, is the causative agent of visceral leishmaniasis. It lives and multiplies within the harsh environment of macrophages. In order to investigate how intracellular parasite manipulate the host cell environment, we undertook a quantitative proteomic study of human monocyte-derived macrophages (THP-1) following infection with<jats:named-content content-type=\"genus-species\">L. donovani<\/jats:named-content>. We used the isobaric tags for relative and absolute quantification (iTRAQ) method and liquid chromatography-tandem mass spectrometry (LC-MS\/MS) to compare expression profiles of noninfected and<jats:named-content content-type=\"genus-species\">L. donovani<\/jats:named-content>-infected THP-1 cells. We detected modifications of protein expression in key metabolic pathways, including glycolysis and fatty acid oxidation, suggesting a global reprogramming of cell metabolism by the parasite. An increased abundance of proteins involved in gene transcription, RNA splicing (heterogeneous nuclear ribonucleoproteins [hnRNPs]), histones, and DNA repair and replication was observed at 24 h postinfection. Proteins involved in cell survival and signal transduction were more abundant at 24 h postinfection. Several of the differentially expressed proteins had not been previously implicated in response to the parasite, while the others support the previously identified proteins. Selected proteomics results were validated by real-time PCR and immunoblot analyses. Similar changes were observed in<jats:named-content content-type=\"genus-species\">L. donovani<\/jats:named-content>-infected human monocyte-derived primary macrophages. The effect of RNA interference (RNAi)-mediated gene knockdown of proteins validated the relevance of the host quantitative proteomic screen. Our findings indicate that the host cell proteome is modulated after<jats:named-content content-type=\"genus-species\">L. donovani<\/jats:named-content>infection, provide evidence for global reprogramming of cell metabolism, and demonstrate the complex relations between the host and parasite at the molecular level.<\/jats:p>","DOI":"10.1128\/iai.02833-14","type":"journal-article","created":{"date-parts":[[2015,2,18]],"date-time":"2015-02-18T08:16:15Z","timestamp":1424247375000},"page":"1853-1868","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":55,"title":["Proteomic-Based Approach To Gain Insight into Reprogramming of THP-1 Cells Exposed to Leishmania donovani over an Early Temporal Window"],"prefix":"10.1128","volume":"83","author":[{"given":"Alok Kumar","family":"Singh","sequence":"first","affiliation":[{"name":"School of Life Sciences, Jawaharlal Nehru University, New Delhi, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rajeev Kumar","family":"Pandey","sequence":"additional","affiliation":[{"name":"Cell Death and Differentiation Research Laboratory, National Institute of Immunology, New Delhi, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jair Lage","family":"Siqueira-Neto","sequence":"additional","affiliation":[{"name":"Institut Pasteur Korea, Seongnam-si, Gyeonggi-do, South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yong-Jun","family":"Kwon","sequence":"additional","affiliation":[{"name":"Institut Pasteur Korea, Seongnam-si, Gyeonggi-do, South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucio H.","family":"Freitas-Junior","sequence":"additional","affiliation":[{"name":"Institut Pasteur Korea, Seongnam-si, Gyeonggi-do, South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chandrima","family":"Shaha","sequence":"additional","affiliation":[{"name":"Cell Death and Differentiation Research Laboratory, National Institute of Immunology, New Delhi, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rentala","family":"Madhubala","sequence":"additional","affiliation":[{"name":"School of Life Sciences, Jawaharlal Nehru University, New Delhi, India"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(98)10178-2"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0169-4758(98)01362-3"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1128\/CMR.18.2.293-305.2005"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1002\/eji.1830250318"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1002\/1521-4141(200111)31:11<3185::AID-IMMU3185>3.0.CO;2-J"},{"key":"e_1_3_3_7_2","doi-asserted-by":"crossref","first-page":"2930","DOI":"10.4049\/jimmunol.152.6.2930","article-title":"Intracellular infection by Leishmania donovani inhibits macrophage apoptosis","volume":"152","author":"Moore KJ","year":"1994","unstructured":"Moore KJ, Matlashewski G. 1994. 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